Fifty shades of graft: How to improve the efficacy of faecal microbiota transplantation for decolonization of antibiotic-resistant bacteria

Background

Spontaneous decolonization of antibiotic-resistant bacteria (ARB) takes time: approximately 25% after 30 days for carbapenem-producing Enterobacteriaceae or extended-spectrum beta-lactamase-producing Enterobacteriaceae. Faecal microbiota transplantation (FMT) has been proposed as a new strategy to promote decolonization in order to reduce the risk of superinfection due to these ARB. This paper discusses the literature on the use of FMT for this indication, and the improvement levers available to promote its efficacy.

Laser‐based radiocarbon detection in the laboratory: How soon?

Research over the past 25 years and the use of accelerator mass spectrometry (AMS) have demonstrated benefits of single‐atom counting of ¹⁴C compared with scintillation monitoring of ¹⁴C radioactive decay for a multitude of applications in drug development studies. These include pharmacokinetics and metabolism studies, microdosing studies, and quantification of DNA adducts. In the last decade, the possibility of single‐atom counting using lasers has been demonstrated, providing the possibility of simplified laboratory‐based systems, which can equal or excel AMS sensitivity and provide scintillation system convenience without high levels of radioactivity. To achieve the required sensitivity, optical storage cavities have been used to enhance the laser interaction of the low densities of radiocarbon present. Two types of laser technologies have been used‐cavity ring‐down spectroscopy (CRDS) and intracavity opto‐galvanic spectroscopy (ICOGS). Problems to be overcome to achieve routine use have included separation of the ¹⁴C signal from backgrounds, achievement of acceptable precision and accuracy, reduction of measurement times for small samples, and improvement in the ease of use for the operator. Both technologies have achieved impressive results to date using samples of order 1 mg with CRDS and 10 μg with ICOGS. Commercial development is the next step.     

Enhanced antitumour activity of doxorubicin and simvastatin combination loaded nanoemulsion treatment against a Swiss albino mouse model of Ehrlich ascites carcinoma

Doxorubicin (DOX) is the most commonly used anticancer drug; however, it has limited use because prolonged administration may result in severe cardiotoxicity. Simvastatin (SIM), generally prescribed for hypercholesterolaemia, has also shown salubrious results in the monotherapy or combinational drug therapy of different cancers in various models. Nanoparticle drug delivery systems are a novel way of improving therapeutics and also improving the absorption and specificity of drugs towards tumour cells. In this study, we exploited this technology to increase drug specificity and minimize imminent adverse effects. In this study, the antitumour activity of the combination formulas of DOX and SIM, either loaded in water (DOX‐SIM‐Solution) or nanoemulsions (NEs) (DOX‐SIM‐NE), was evaluated in a Swiss albino mouse model of Ehrlich ascites carcinoma. The anticancer effect was assessed by quantifying the change in body weight, mean survival time, and percent increase in lifespan (%ILS), determining haematological and serum biochemical parameters (liver function test, kidney function test and lipid profile parameters) as well as studying the histopathological alterations in liver tissues. We observed a clear increase in %ILS of the DOX‐SIM‐Solution group (265.30) that was double the %ILS of the DOX‐SIM‐NE group (134.70). However, DOX‐SIM‐NE had a non‐toxic effect on the haematological parameters, whereas DOX‐SIM‐Solution increased the levels of haemoglobin and lymphocytes. Furthermore, the encapsulation of SIM and DOX into NEs improved the levels of all serum biochemical parameters compared to the DOX‐SIM‐Solution. A reduction in the side effects of DOX‐SIM‐NE on the liver was also established using light microscopy, which revealed that the morphologies of the hepatocytes of the mice were less affected by administration of the DOX‐SIM‐NE treatment than with the DOX‐SIM‐Solution treatment. The study showed that incorporating SIM into the DOX‐loaded‐NE formulation remarkably improved its efficiency and simultaneously reduced its adverse effects.     

Rapid remodeling of the maxillary sinus in silent sinus syndrome

Silent sinus syndrome (SSS) is a rare disorder involving bony remodeling of the maxillary sinuses, including collapse of the orbital floor. It is typically unilateral and seen in the setting of chronic maxillary sinusitis. Patients present with enophthalmos and hypoglobus occasionally accompanied by diplopia. The condition is generally diagnosed with CT imaging and treated surgically. While SSS is most often reported as very slowly progressive, we report a patient with evidence of significant remodeling of the maxillary sinus over a period of 5.5 months.     

Temperature-controlled power modulation compensates for heterogeneous nanoparticle distributions: a computational optimization analysis for magnetic hyperthermia

Purpose: To study, with computational models, the utility of power modulation to reduce tissue temperature heterogeneity for variable nanoparticle distributions in magnetic nanoparticle hyperthermia.

Methods: Tumour and surrounding tissue were modeled by elliptical two- and three-dimensional computational phantoms having six different nanoparticle distributions. Nanoparticles were modeled as point heat sources having amplitude-dependent loss power. The total number of nanoparticles was fixed, and their spatial distribution and heat output were varied. Heat transfer was computed by solving the Pennes’ bioheat equation using finite element methods (FEM) with temperature-dependent blood perfusion. Local temperature was regulated using a proportional-integral-derivative (PID) controller. Tissue temperature, thermal dose and tissue damage were calculated. The required minimum thermal dose delivered to the tumor was kept constant, and heating power was adjusted for comparison of both the heating methods.

Results: Modulated power heating produced lower and more homogeneous temperature distributions than did constant power heating for all studied nanoparticle distributions. For a concentrated nanoparticle distribution, located off-center within the tumor, the maximum temperatures inside the tumor were 16% lower for modulated power heating when compared to constant power heating. This resulted in less damage to surrounding normal tissue. Modulated power heating reached target thermal doses up to nine-fold more rapidly when compared to constant power heating.

Conclusions: Controlling the temperature at the tumor-healthy tissue boundary by modulating the heating power of magnetic nanoparticles demonstrably compensates for a variable nanoparticle distribution to deliver effective treatment.